Effect of oral contraceptive progestins on serum copper concentration

Eur J Clin Nutr. 1998 Oct;52(10):711-5. doi: 10.1038/sj.ejcn.1600631.


Objectives: Recent epidemiologic studies have shown an increased mortality from cardiovascular diseases in people with higher serum copper levels. Even though higher serum copper concentration in women using oral contraceptives is well known, there is still uncertainty about the influence of newer progestin compounds in oral contraceptives on serum copper concentration. This issue is of particular interest in the light of recent findings of an increased risk of venous thromboembolism in users of oral contraceptives containing newer progestins like desogestrel compared to users of other oral contraceptives.

Design: Cross-sectional epidemiologic study. Examinations included a detailed questionnaire on medical history and lifestyle factors, a seven day food record, and blood samples.

Setting: National health and nutrition survey among healthy people living in private homes in West Germany in 1987-1988.

Subjects: Nonpregnant and nonlactating women aged 18-44 y (n = 610).

Results: Overall, the use of oral contraceptives was positively associated with serum copper concentration in by bi- and multivariable linear regression models with log-transformed values of serum copper concentration as dependend variable and oral contraceptive preparations and potential confounding variables as independent variables. Serum copper concentration in women using oral contraceptives varied more strongly by different progestin compounds than by estrogen contents. The highest increase of serum copper was seen in women using oral contraceptives containing antiandrogen progestins (55%; 95% CI: 37-76%), followed by desogestrel (46%; 95% CI: 36-56%), norethisteron/lynestrenol (42%; 95% CI: 29-57%), and levonorgestrel (34%; 95% CI: 24-45%).

Conclusion: While elevated serum copper concentration was found in users of all types of oral contraceptives, elevation was more pronounced among women taking oral contraceptives with antiandrogen effective progestins like antiandrogens or third generation oral contraceptives containing desogestrel. Further investigation is required to shed light on the possible role of high serum copper concentration in increasing cardiovascular or thrombotic risk of women using oral contraceptives.

PIP: High serum copper concentration--a well-known effect of oral contraceptive (OC) use--has been linked to increased mortality from cardiovascular disease. The influence of OCs containing newer progestins has not been investigated, however. This concern was addressed in a 1987-88 cross-sectional epidemiologic study of 610 nonpregnant, nonlactating West German women 18-44 years of age. 195 women (32.1%) were current OC users, but only 152 of these women were able to cite the name of the formulation they were taking. In 70% of cases, the OC contained less than 45 mcg of ethylestradiol (median dose, 32.4 mcg). The most common progestin components were desogestrel (41%) and levonorgestrel (30%). Mean serum copper concentration was higher among users of all types of OCs than among non-users, but this concentration varied more strongly according to the OC's progestin compound than its estrogen content. The greatest increase in serum copper (55% compared with non-users) was recorded in users of OCs containing anti-androgen progestins, followed by desogestrel (46%), norethisterone/lynestrenol (42%), and levonorgestrel (34%). The increase in serum copper was more pronounced in women taking OCs containing 45 mcg or less of ethylestradiol than in users of OCs with a high estrogen dose. In the regression models, the different progestin compounds alone explained 28% of the total variance in serum copper concentration. Further investigation of OC-induced increases in serum copper concentration and their impact on cardiovascular risk are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Androgen Antagonists / adverse effects
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / chemically induced
  • Contraceptives, Oral / adverse effects*
  • Copper / blood*
  • Cross-Sectional Studies
  • Desogestrel / adverse effects
  • Female
  • Humans
  • Levonorgestrel / adverse effects
  • Norethindrone / adverse effects
  • Progesterone Congeners / adverse effects
  • Progestins / adverse effects*
  • Surveys and Questionnaires


  • Androgen Antagonists
  • Contraceptives, Oral
  • Progesterone Congeners
  • Progestins
  • Levonorgestrel
  • Copper
  • Desogestrel
  • Norethindrone